The gene for the nuclear phosphoprotein p53 is the most commonly mutated gene yet identified in human cancers (Vogelstein, B., Nature, 348:681 (1990)). Missense mutations occur in tumors of the colon, lung, breast, ovary, bladder, and several other organs (S. J. Baker, et al., Science, 244:217 (1989); J. M. Nigro, et al., Nature, 342:705 (1989); T. Takahashi, et al., Science, 246:491 (1989); Romano, et al., Oncogene, 4:1483 (1989), Menon, Proc. Natl Acad. Sci. USA, 87:5435 (1990); Iggo, et al., Lancet ii, 675 (1990); T. Takahashi, et al., J. Clin. Invest. 86:363 (1990); Mulligan, Proc. Natl Acad. Sci. USA, 87:5863 (1990); Bartek, et al., Oncogene, 5:893 (1990); Stratton et al., Oncogene, 5:1297 (1990)). One of the important challenges of current cancer research is the elucidation of the biochemical properties of the p53 gene product and the way in which mutations of the p53 gene affect these properties.
Although some biological characteristics of p53 have been defined, such as its ability to suppress the growth of in vitro transformed murine cells (Eliyahu, et al., Proc. Natl Acad. Sci. USA 86:8763 (1989); Finlay, et al., Cell, 577:1083 (1989)) or human cancer cells (Baker, et al., Science, 249:912 (1990); Mercer, et al., Proc. Natl Acad. Sci, USA, 87:6166 (1990); Diller et al., Mol. Cell Biol. (1990)), the biochemical basis of this suppression remains largely unknown. As a step towards understanding such properties, we have attempted to determine whether p53 binds to specific DNA sequences within the human genome.